Modifying the diet of pregnant and nursing mice can increase their offspring's risk of developing colitis (inflammation of the large bowel, a model of human inflammatory bowel diseases). The composition of mother's food can influence the levels of gene expression in the pups in association with modifying the epigenome and the microbiome of their large intestine, said researchers at Baylor College of Medicine in a report in the current edition of the journal of Human Molecular Genetics.

"We know that the intestinal microbiota (microorganisms that reside in our body) plays a role in these conditions, and that the disorders are modulated by genetic predisposition and environmental factors," said Dr. Richard Kellermayer, assistant professor of pediatric gastroenterology at BCM and co-author of the report. "What we don't know is how prenatal and early developmental environmental exposures affect the microbiome and the immune system and how those may predispose us to inflammatory bowel diseases (Crohn's disease and ulcerative colitis)."

The question is important because of the significantly increasing incidence of inflammatory bowel diseases in the developed world, said Kellermayer.

Influencing susceptibility

Kellermayer and his colleagues focused on a specific diet that is supplemented with micronutrients and vitamins commonly used in human prenatal supplements. These supplements were folate, methionine, betaine and vitamin B12. The diet is designated as a methyl-donor diet. It has been observed that this diet can modify the methylation of DNA at specific regions. This molecular change is stable and can influence the expression of genes. Gene expression changes can lead to modified body characteristics. For instance, modified gene expression may make an individual more prone to develop this disease. Therefore, it has been proposed that dietary changes at critical stages of development may modify DNA methylation, thereby influencing our susceptibility to develop common disorders, such as inflammatory bowel disease.

Researchers fed pregnant mice the methyl-donor diet or a control diet during pregnancy and while their pups were nursing. Once the pups were weaned, they were put on a control or normal diet. Those on the methyl-donor diet were exposed to it only through their mothers.

"We found that the animals exposed to the methyl-donor diet through their moms during their very early development were more susceptible to colitis even in young adulthood. In fact, about 30 to 40 percent suffered extreme weight loss," said Kellermayer.

Long-term effects

Researchers also looked at the long-term effects of the dietary exposure on large intestinal DNA methylation and the microbiome. Mice were examined at 30 days and then again at 90 days after birth. Kellermayer said there was a significant difference in the epigenome (genome wide DNA methylation in this case) and the microbiome of those who were exposed to the methyl-donor diet compared to those who were not.

"Because the methyl donor diet includes common components of prenatal dietary supplements, we feel that the results of this experiment could be of great significance for future guidelines for judicious prenatal vitamin use. However, it is too early to associate these results with humans," he said.

Others who took part in the study include: Drs. Tiffany D. Schaible and C. Wayne Smith, both of the Department of Pediatrics at BCM, Texas Children's Hospital, and the USDA/ARS Children's Nutrition Research Center at Baylor College of Medicine; Dr. R. Alan Harris, Department of Molecular and Human Genetics at BCM and Scot E. Dowd, Research and Testing Laboratory in Lubbock, TX.

Funding for this study came from the Crohn's and Colitis Foundation of America, the Children's Digestive Health and Nutrition Foundation, the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition, the Broad Medical Research Program of the Broad Foundation, the National Human Genome Research Institute, and the U.S. Department of Agriculture/Agriculture Research Service.